Prostate cancer was the most commonly diagnosed cancer in males (217,730 new cases) and the second leading cause of cancer-related death among men (32,050 fatalities) in the United States in 2010.1 Upon diagnosis by current detection regimens, about 30% of patients have metastases.2,3 Approximately 50% of patients eventually develop metastases.4 Survival times for patients with metastases are generally 2˜3 years from the time when the metastases are diagnosed.5 Unfortunately, current prostate cancer treatments (radical prostatetectomy, chemotherapy, immunotherapy, hormonal therapy and radiation therapy) are far from satisfactory and no curative treatment exists for metastatic prostate cancer. Early diagnosis of prostate cancer is critical for appropriate treatment decisions and may provide the patients the best opportunities for cures or prolonged survivals.
Currently, prostate-specific antigen (PSA) test is the first-line clinical screening tool for prostate cancer. However, PSA test is lack of sensitivity and specificity since PSA is an organ-specific biomarker rather than a cancer-specific biomarker. Approximately 43% of patients with organ-confined prostate cancer do not have elevated PSA levels,6 indicating the high percentage false-negative rate of the PSA test. On the other hand, benign prostatic hyperplasia (BPH), which is extremely common in men, commonly results in elevated PSA levels.7 Hence, PSA test has 60-80% false-positive findings based on prostate biopsies.8 
The clinical single photon emission computed tomography (SPECT) scan using 111In-capromab Pendetide (ProstaScint® Scan, Cyt-356) targeting the prostate-specific membrane antigen (PSMA) provides more accurate localization and staging of a new or recurrent prostate cancer than the PSA test.9-12 However, relatively low sensitivity (62%) and overall accuracy (68%) of the ProstaScint scan limits its widespread application. At present, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is the most commonly used positron emission tomography (PET) imaging agent for the detection of various tumors including prostate cancer.13-16 However, the delineation of prostate cancer by PET with [18F]FDG is generally unsatisfactory due to the low uptake of [18F]FDG in prostate cancer.15,16 Relatively low sensitivity (60-70%) of [18F]FDG PET is due to the fact that the glucose utilization is not significantly higher in prostate cancer cells than that in normal cells. The limited clinical application of ProstaScint® and [18F]FDG underscores the urgent need for novel cancer-specific imaging probes for prostate cancer detection.
Over-expression of gonadotropin-releasing hormone (GnRH) receptors on prostate cancer cells and specimens, dramatic low level expression on healthy prostate cells and no expression on most normal tissue cells17-25 highlights the potential of GnRH receptor as a distinct molecular target for developing novel prostate cancer-specific imaging probes. Nativ GnRH peptide is a peptide with 10 amino acids (pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH2 SEQ ID NO:1). Both pGlu1-His2-Trp3 and Arg8-Pro9-Gly10-NH2 motifs are crucial for GnRH receptor binding.26 A backbone metal cyclization between the N-terminus and C-terminus of the GnRH peptides dramatically decreased their GnRH receptor binding affinities,27 confirming that both N-terminus and C-terminus need to be reserved for strong GnRH receptor binding. The replacement of Gly6 with a D-amino acid enhanced the binding affinity and reduces the metabolic clearance of the peptide.28 
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women in the United States. It was predicted that approximately 209,060 new cases would be diagnosed and 40,230 fatalities would occur in the US in 20101. Unfortunately, no curative treatment exists for metastatic breast cancer. Early diagnosis of breast cancer followed by a prompt surgical removal provides patients the best opportunities for cures or prolonged survivals. Mammography is an effective diagnostic tool for primary breast cancer. However, it is less effective for women with breast implants, post-surgical recurrence, or for women under age fifty as the breast tissue tends to be more dense2. Meanwhile, the mammography can't detect distant breast cancer metastases. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques3,4 are more attractive non-invasive imaging modalities for metastatic breast cancer detection due to their high sensitivities and spatial resolutions. At present, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is the most commonly used PET imaging agent for the detection of various tumors including breast cancer5-15. However, the clinical application of [18F]FDG is limited10 by its unsatisfactory sensitivity for small tumors <1 cm (57%) and for tumors in-situ (25%), and high false-positive results in the circumstance of inflammation. Hence, novel breast cancer-specific imaging probes are urgently needed to improve the detection accuracy for breast cancer.
As in the case of breast cancer, the over-expression of gonadotropin-releasing hormone (GnRH) receptors on the breast cancer cells16-20 highlights the potential of GnRH receptor as a molecular target for developing breast cancer-specific imaging probes. Clinical studies shows that 52% of breast cancer specimens removed by surgical resection over-expressed GnRH receptors19-20. Native GnRH peptide is a hypothalamic decapeptide (pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH2 SEQ ID NO:1). Both motifs of pGlu1-His2-Trp3 and Arg8-Pro9-Gly10-NH2 motifs are critical for GnRH. receptor binding.26 The replacement of Gly6 with a D-amino acid increases the binding affinity and decreased the metabolic clearance of the peptide22. The D-Lys6-GnRH peptide has been used as a delivery vehicle to target the chemotherapy agent (2-pyrrolino-doxorubicin, AN201) to the GnRH receptors for breast cancer treatment23-31. The AN201 was coupled to the epsilon amino group of D-Lys6 in D-Lys6-GnRH to generate a cytotoxic compound named AN20723. The receptor-targeting AN207 exhibited enhanced remarkable therapeutic efficacy and decreased toxicity compared to the parent chemotherapy agent AN201. A single treatment of AN207 (250 nmol/kg) resulted in 100% cure for the mice bearing MX-1 human mammary carcinomas (GnRH receptor-positive) without apparent toxicity28. These results on AN207 indicated that D-Lys6-GnRH could selectively bind the GnRH receptor to target the chemotherapy agent to breast cancer cells. The Present inventors have been interested in. developing radiolabeled GnRH peptides to target the GnRH receptors for cancer detection.29 To that end, they provide the various aspects of the present invention.